acute effect of pulmonary desufflation on cardiac performance in copd patients

Conditions: COPD; Hyperinflation; Right Cardiac Failure

Summary: chronic obstructive pulmonary disease (copd) is one of the major clinical entities that causes thousands of deaths every year all over the world and weights a lot on the health care system of every country in terms of direct and indirect costs. the physiopathological modifications that characterise copd are represented by irreversible (sometimes partially reversible) airflow obstruction, and bronchiolar inflammation. lungs that develop emphysema lack of elastic recoil and imply increased resistances and airflow obstruction due to loss of lung parenchyma and supporting elastic structures. all these modifications produce air trapping and so lung hyperinflation. the latter is precisely the cause of the symptoms and particularly dyspnoea which is often heavily perceived by copd patients and that drives to the limitation of daily activities. lung hyperinflation and the other alterations that occur in copd imply gas retention and increase in pulmonary vascular resistances. considering that the rib cage has limited elastic properties, the effects of gas trapping and lung parenchymal damage on mediastinum and particularly on heart mechanics is indisputable. together with alveolar hypoxia, lung hyperinflation is responsible for the development, as the disease progresses, of the cor pulmonale. tha latter causes pulmonary hypertension and increased mechanic load during right heart chambers contraction and relaxation. those alterations may effect left heart chambers too. airflow obstruction in copd is usually treated by inhaled bronchodilators and corticosteroids. the main and most used bronchodilators are represented by beta 2 agonists (short, long and ultra-long acting) and anticholinergic inhalatory drugs, which can be also short, long and ultra long acting. among ultra long acting beta 2 agonists, indacaterol is characterised by quick onset of action (5 minutes), and guarantees an effective bronchodilation duration of 24 hours. it is also known that it has an important effect on reducing lung hyperinflation decreasing residual volume and consequently allowing an increase of inspiratory capacity. the purpose of our study is to evaluate the effects of indacaterol on lung hyperinflation in copd subjects of any stage and with lung air trapping, and the consequent potential effects on heart performance evaluated by cardiac trans thoracic echo color doppler.

in a paper recently published, barr et al, supposed that pulmonary emphysema and bronchial obstruction were inversely related with ventricular telediastolic volume, with the ejection volume and the ejection fraction in patients with severe pulmonary disease. the mechanisms that are involved in the development of cor pulmonale are the increase of pulmonary vascular resistances, lung hyperinflation and hypoxic vascular constriction. all the mentioned contribute to the generation of right cardiac failure and consequently, left cardiac failure. the authors assessed lung hyperinflation by ct scan, pulmonary function by spirometry, and cardiac kinetic and mechanics by magnetic resonance. they concluded that the amount of emphysema and bronchial obstruction were related with a worse telediastolic left ventricular volume and stroke volume, no relation was found with ejection fraction. it was evident that patients with severe pulmonary disease and with no present cardiac diseases, had sub-clinic modifications that one day may lead them to the development of cor pulmonale. the effect of bronchodilation, with its effect on lung hyperinflation, may have a role in producing some modifications in this context. that's why that the aim of our study is centered on the evaluation of the effect of bronchodilation firstly on diastolic right ventricular function and also on interventricular septum motility, on the ejection fraction and on the kinetics of right cardiac chambers assessed by cardiac echocardiography

Eligibility criteria:
inclusion criteria: * signature of informed consent * copd patients with age raging from 50 to 85 years old * patients with at least a history of copd of one year * copd patients clinically stable in the last three months * copd subjects with fev1 (forced expiratory volume at one second)\<70% of predicted value * fev1/fvc (forced vital capacity)\<88% (males) or \<89% (females) of lln (lower levels of normality) * copd former or active smokers with at least a smoking history of 20 pack years * residual volume (rv) \>= 125% predicted value * no cardiac ultrasound signs of cor pulmonale exclusion criteria: * acute bronchial exacerbation at recruitment * fertile women with age between 18 and 50 years old or with active period * pregnancy * subjects enrolled in other clinical trials or that have taken part in one of them in the month preceding the enrollment. * fev1/fvc more than 70% of predicted value in basal conditions * fev1 more than 70% of predicted value in basal conditions * residual volume \< 125% predicted value * known deficit of alpha 1 antitrypsin * subjects that underwent a lung volume reduction surgery (lvrs) * subjects with known positivity to human immunodeficiency virus (hiv) * misuse of alcool or drugs * lack of compliance in performing respiratory tests * subjects not capable to follow the study prescriptions because of psychic disorders or language problems. * long term oxygen therapy with flows \> 6 litres per minute (l/min) at rest * cor pulmonale * patients that cannot take indacaterol for cardiologic reasons

Keywords: copd pulmonary hyperinflation ultra long acting beta 2 agonists cor pulmonale cardiac performance